Human chromosome 21 is the smallest human chromosome which comprises about 1.4% od human genome. In the last five years, many DNA polymorphisms have been mapped to this chromosome and two genetic linkage maps have been developed using large reference pedigrees. The average distance between DNA markers in the existing linkage maps is 6- 10 Cm. However, not all mapped DNA markers are adequately informative, easy to score and available, and few can be typed using the polymerase chain reaction. The goal of this proposal is to create a detailed linkage map of human chromosome 21 using index DNA markers that are highly informative (Het greater than 0.60) can be preferably typed with PCR and their density on chromosome 21 is such that the average distance between adjacent markers is less than 5 Cm.